Methylphenidate (RITALIN), a piperidine derivative, is commonly prescribed for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). Alarmingly, recent data from the Drug Enforcement Agency (DEA) indicate that methylphenidate (METH) abuse is widespread and represents a significant public-health concern. For example, between 1989 and 1993 emergency-room admissions involving METH increased by as much as 715%. There is accumulating evidence that the symptoms of childhood ADHD persist into adulthood in a significant number of cases, and adulthood ADHD is associated with high rates of psychiatric comorbidity, including cocaine (COC) abuse. Whether COC abusers with ADHD are at risk to abuse METH is unclear, and many clinicians are reluctant to prescribe stimulants to these patients because of their histories of COC abuse. The specific aim of this project is to rigorously characterize the abuse potential of METH, the most commonly prescribed medication for the treatment of childhood and adulthood ADHD. To accomplish this aim, 3 inpatient, laboratory experiments will be conducted with volunteers with histories of COC abuse. Exp. 1 will replicate and extend findings from a previous study conducted in our laboratory that showed the discriminative-stimulus and subjective effects of METH are indistinguishable from those of COC. Exp. 2 will determine the relative reinforcing effects of METH and COC. Exp. 3 will determine the influence of rate of onset on the reinforcing, subjective and physiological effects of drugs by examining the effects of sustained- and immediate- release METH. We have two primary hypotheses. First, METH and COC will produce positive subjective effects and function as reinforcers. METH and COC will differ in terms of potency, but not efficacy. Second, sustained- release METH will have less abuse potential than immediate-release METH. The experiments proposed in the present application have at least 3 basic science and clinical implications. First these experiments will determine the abuse potential of METH in individuals with histories of COC abuse. Second, these experiments will determine whether decreasing the rate of onset of METH's effect reduces its abuse potential. Rate of onset is thought to be an important determinant of a drug's abuse potential. Third, these experiments may identify compounds that have reduced abuse potential (e.g., sustained-release METH) and may guide the pharmacological treatment of COC abusers with ADHD. The proposed experiments will also allow us to assess the effects of participating in non-treatment, inpatient, drug-abuse studies and to conduct retrospective analysis to determine the influence of individual differences (e.g., amount of cocaine use, amount and kind of other drug use, gender, ethnicity, socioeconomic status, as well as scores on a structured mental status exam, the Wender-Utah Rating Scale, the Beck Depression Inventory and several measures of personality function) on the behavioral and physiological responses to stimulants.